OBJECTIVES:

Lurbinectedin received accelerated FDA approval for patients with metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy based on results from a single-arm basket trial (NCT02454972). We conducted a systematic literature review (SLR) to evaluate clinical trials of second-line SCLC therapies recommended by NCCN Guidelines and assessed the feasibility of an indirect treatment comparison (ITC) to estimate relative efficacy and safety of lurbinectedin versus relevant comparators.

METHODS:

Predefined searches of published and unpublished data were executed on January 6, 2021. Eligible non-randomized and single-arm trials were included only when comparative randomized controlled trials (RCTs) were unavailable for an intervention of interest. Two independent reviewers conducted abstract/full-text selection and data extraction.

RESULTS:

Of 4,769 citations identified, 10 unique relevant trials were included (5 RCTs, 2 single-arm trials, 2 RCTs with 1 arm of interest, and 1 with randomized and non-randomized cohorts with 1 arm of interest). Although there were differences in proportions of patients with sensitive/resistant disease, ECOG status, and limited/extensive disease, other baseline characteristics were generally consistent. Nine trials included patients with both limited- and extensive-stage disease at diagnosis. Three trials enrolled patients with platinum-sensitive disease (chemotherapy-free interval [CTFI] ≥90 days), 6 trials included patients with sensitive and resistant disease (CTFI <90 days); 1 trial did not report sensitivity. Only 5 trials included >10% of patients with resistant disease. In platinum-sensitive disease, median overall survival was between 5.8 and 8.1 months for topotecan (IV or oral), 7.5 months for platinum-rechallenge, and 11.9 months for lurbinectedin.

CONCLUSIONS:

These SLR results suggest that an ITC is feasible, as required assumptions are not prohibitive. Population-adjusted ITCs are required to adequately compare lurbinectedin with other treatments, given the inclusion of several disconnected single-arm trials. Restricting the ITC to patients with platinum-sensitive disease (CTFI ≥90 days) would reduce heterogeneity.